Bolduc, Veronique (NINDS)
Muntoni, Francesco (UCL Business PLC)
Wilton, Steve (Murdoch University)
MacArthur, Daniel (The General Hospital Corporation)
Monkol, Lek (The General Hospital Corporation)
Cumming, Beryl (President and Fellows of Harvard College)
This invention includes the identification of a new mutation in the collagen type VI (COL6A1) gene, including a method for diagnosing and treating patients with this mutation. Collagen type VI-related dystrophies (COL6-RD) are devastating neuromuscular disorders that manifest with progressive generalized muscle weakness, contractures, and respiratory failure. Currently, no cure exists for COL6-RD. In addition, despite the effectiveness of current targeted genetic testing methods to detect many of the mutations causing COL6-RD, there are still a large number of patients presenting with clinical and biochemical features of COL6-RD, but without any identified mutations. Our novel identification includes a mutation in intron 11 of the COL6A1 gene that alters the splicing of the gene pre-mRNA and produces a mature alpha 1 (VI) chain mRNA that comprises an additional exon. We describe a method for diagnosing this mutation, as well as a method for specifically treating this mutation using exon-skipping technologies.
Currently, no cure exists for COL6-RD. In addition, despite the effectiveness of current targeted genetic testing methods to detect most of the mutations causing COL6-RD, there is still a large number of patients presenting with clinical and biochemical features of COL6-RD, but for whom no mutations have been identified indicating that current methods of diagnosing and treating COL6-RD are insufficient. We found this particular mutation to be the single most common individual mutation in our COL6-RD cohort.